PB2083: STUDY CONDUCT AND PATIENT SAFETY DURING THE COVID-19 PANDEMIC: OBSERVATIONS IN PATIENTS WITH PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA FROM THE GAZELLE TRIAL OF OBINUTUZUMAB SHORT DURATION INFUSION
Authors: M. A. Canales, T. A. Buchholz, T. Ishikawa, L. M. Fogliatto, J. Bortolini, F. J. Capote Huelva, A. Salar, D. Tucker, E. Vorozheikina, D. Klingbiel, S. Pokala, J. Parreira, S. Nick, K. Hübel
Journal: HemaSphere (2022)

Background: Obinutuzumab is routinely administered as a 3–4-hour infusion in patients (pts) with follicular lymphoma (FL). A 90-minute short duration infusion (SDI) of obinutuzumab is being evaluated in GAZELLE (NCT03817853), a Phase IV study in pts with previously untreated FL. Earlier analyses showed that response rates with obinutuzumab SDI were in line with previous studies of obinutuzumab administered at the standard rate and no new safety signals were reported (Canales, et al. 2021). In addition, >95% of healthcare providers preferred obinutuzumab SDI to the standard infusion, mainly due to clinic and pt time savings (Trask, et al. 2021). The time savings associated with obinutuzumab SDI could be particularly beneficial during the coronavirus disease 2019 (COVID-19) pandemic. Aims: To investigate the effect of the COVID-19 pandemic on the GAZELLE study conduct and to describe safety in vaccinated and unvaccinated pts in an exploratory analysis. Methods: Pts with previously untreated FL received obinutuzumab (1000mg) intravenously on Days (D) 1, 8 and 15 of Cycle (C) 1, and on D1 thereafter, plus chemotherapy (bendamustine; cyclophosphamide, doxorubicin, vincristine and prednisone [CHOP]; or cyclophosphamide, vincristine and prednisone [CVP]) for 6–8 cycles (induction phase). Pts received a standard infusion (3–4 hours) of obinutuzumab in C1. Pts without a Grade ≥3 infusion-related reaction during C1 received obinutuzumab SDI (90-minute infusion) from C2 onwards. Pts with a complete or partial response received maintenance with obinutuzumab SDI for 2 years or until disease progression (maintenance phase). All pts provided informed consent prior to study entry. Results: At the clinical cut-off date of January 18, 2022, 35/113 (31.0%) pts in the overall population had received a COVID-19 vaccine. Demographic and baseline characteristics were generally similar in the vaccinated and non-vaccinated groups; however, the vaccinated group had a greater proportion of pts who were aged ≥65 years (n=17/35, 48.6% vs n=27/78, 34.6%, respectively). The most common vaccine received was Pfizer BioNTech (n=22/35, 62.9%), and most pts received 2 vaccine doses (n=25/35, 71.4%). Fewer study discontinuations were reported in the vaccinated versus the non-vaccinated group (n=1 vs n=21, Figure). Five pts in the vaccinated group had adverse events (AEs) ≤7 days after vaccination (no serious AEs reported). None of these AEs were considered study drug related and all resolved without changes to study treatment. COVID-19 infection was reported in 5 pts (induction phase, n=1; maintenance phase, n=4). Of these, 1 pt had been vaccinated (Moderna, 2 doses; >6 months prior to infection) and 3 pts received concomitant medication to treat COVID-19 infection. Three of the 5 pts recovered, and 2 pts (both unvaccinated) died due to respiratory complications following COVID-19 infection. Low total leukocyte count (an indicator of COVID-19 disease severity) was observed in 4 pts with a COVID-19 infection (7 episodes of Grade 1/2; 3 episodes of Grade 3). Overall, 19/113 (16.8%) pts had ≥1 major protocol deviation related to the COVID-19 pandemic, the most common being delayed (n=8) or missed (n=7) study drug infusion. Image:Summary/Conclusion: The conduct of the GAZELLE study was not substantially impacted by the COVID-19 pandemic. Documented COVID-19 infections occurred in 5 pts and fatal outcomes were reported in 2 of these pts (both unvaccinated). Up to 7 days after COVID-19 vaccination, no AEs considered related to obinutuzumab or other study treatments were observed.